1-147242720-C-G

Position:

• chr1-147242720-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004284.6(CHD1L):​c.17C>G​(p.Ala6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHD1L NM_004284.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0520

Genes affected

CHD1L (HGNC:1916): (chromodomain helicase DNA binding protein 1 like) This gene encodes a DNA helicase protein involved in DNA repair. The protein converts ATP to add poly(ADP-ribose) as it regulates chromatin relaxation following DNA damage. Overexpression of this gene has been linked to several types of cancers. [provided by RefSeq, Feb 2017]

FMO5 (HGNC:3773): (flavin containing dimethylaniline monoxygenase 5) Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

ENSG00000237188 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10596222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD1L	NM_004284.6	c.17C>G	p.Ala6Gly	missense_variant	1/23	ENST00000369258.8	NP_004275.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD1L	ENST00000369258.8	c.17C>G	p.Ala6Gly	missense_variant	1/23	1	NM_004284.6	ENSP00000358262.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.17C>G (p.A6G) alteration is located in exon 1 (coding exon 1) of the CHD1L gene. This alteration results from a C to G substitution at nucleotide position 17, causing the alanine (A) at amino acid position 6 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.0091	T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.10	N;N
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.60	T;.
Polyphen		0.18	B;B
Vest4		0.090
MutPred		0.33		Gain of methylation at R3 (P = 0.1042);Gain of methylation at R3 (P = 0.1042);
MVP		0.60
MPC		0.040
ClinPred		0.30	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.028
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1665087556; hg19: chr1-146714370;